Comparison of Apolipoprotein and Proteoglycan Deposits in Human Coronary Atherosclerotic Plaques

Abstract

Background —Because the content of specific proteoglycans and apolipoproteins is increased in atherosclerotic plaques and in vitro studies have suggested a role for proteoglycans in mediating plaque apolipoprotein (apo) retention, immunohistochemistry was performed to systematically examine the relative locations of proteoglycans and apolipoproteins in human atherosclerosis. Methods and Results —The spatial relationships of versican, biglycan, and apoE were compared on 68 human coronary artery segments; apoA-I and apoB also were evaluated on an additional 20 segments. Nonatherosclerotic intima contained extensive deposits of versican, whereas deposits of apoE, apoB, and apoA-I were much less prevalent. In contrast, nearly all atherosclerotic segments contained substantial deposits of biglycan, apoE, apoA-I, and apoB. There was a high degree of colocalization of apoE and biglycan deposits. ApoA-I, the major apolipoprotein of HDL, and apoB also were detected in regions with apoE and biglycan deposition. Exceptions to the localization of biglycan with apolipoproteins were found in regions that lacked intact extracellular matrix because of necrosis or dense macrophage accumulation. In vitro studies demonstrated that biglycan binds apoE-containing but not apoE-free HDL and that biglycan also binds LDL. Conclusions —These results suggest that biglycan may bind apoE and apoB in atherosclerotic intima. They also raise the possibility that apoE may act as a “bridging” molecule that traps apoA-I–containing HDL in atherosclerotic intima. Taken together, these findings are consistent with the hypothesis that biglycan may contribute to the pathogenesis of atherosclerosis by trapping lipoproteins in the artery wall.